scholarly journals Untypical Metabolic Adaptations in Spontaneously Hypertensive Rats to Free Running Wheel Activity Includes Uncoupling Protein-3 (UCP-3) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Annemarie Wolf ◽  
Hanna Sarah Kutsche ◽  
Felix Atmanspacher ◽  
Meryem Sevval Karadedeli ◽  
Rolf Schreckenberg ◽  
...  
Keyword(s):  
Physical Activity ◽  
Hypertensive Rats ◽  
Running Wheel ◽  
Spontaneously Hypertensive ◽  
Glut 1 ◽  
Hepatic Expression ◽  
Glut 4 ◽  
Metabolic Adaptations ◽  
Free Running ◽  
Wheel Activity

Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of UCP-2, UCP-3, GLUT-4, and PCSK9. Hypertension was associated with lower levels of UCP-2 and PCSK9 mRNA in the M. gastrocnemius, but increased expression of GLUT-1 and GLUT-4 in the M. soleus. Exercise down-regulated UCP-3 in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of UCP-2 in the M. soleus. Exercise increased the expression of GLUT-1 in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine IL-6 and that of GLUT-1 were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.

scholarly journals Pro-inflammatory Vascular Stress in Spontaneously Hypertensive Rats Associated With High Physical Activity Cannot Be Attenuated by Aldosterone Blockade

2021 ◽  
Vol 8 ◽  
Author(s):  
Rolf Schreckenberg ◽  
Annemarie Wolf ◽  
Christian Troidl ◽  
Sakine Simsekyilmaz ◽  
Klaus-Dieter Schlüter
Keyword(s):  
Physical Activity ◽  
Vascular Wall ◽  
Hypertensive Rats ◽  
Running Wheel ◽  
Spontaneously Hypertensive ◽  
High Physical Activity ◽  
Beneficial Effects ◽  
Voluntary Running ◽  
Running Wheel Exercise ◽  
Wheel Activity

The effect of high physical activity, performed as voluntary running wheel exercise, on inflammation and vascular adaptation may differ between normotensive and spontaneously hypertensive rats (SHRs). We investigated the effects of running wheel activity on leukocyte mobilization, neutrophil migration into the vascular wall (aorta), and transcriptional adaptation of the vascular wall and compared and combined the effects of high physical activity with that of pharmacological treatment (aldosterone antagonist spironolactone). At the start of the 6th week of life, before hypertension became established in SHRs, rats were provided with a running wheel over a period of 10-months'. To investigate to what extent training-induced changes may underlie a possible regression, controls were also generated by removal of the running wheel for the last 4 months. Aldosterone blockade was achieved upon oral administration of Spironolactone in the corresponding treatment groups for the last 4 months. The number of circulating blood cells was quantified by FACS analysis of peripheral blood. mRNA expression of selected proteins was quantified by RT-PCR. Histology and confocal laser microscopy were used to monitor cell migration. Although voluntary running wheel exercise reduced the number of circulating neutrophils in normotensive rats, it rather increased it in SHRs. Furthermore, running wheel activity in SHRs but not normotensive rats increased the number of natural killer (NK)-cells. Except of the increased expression of plasminogen activator inhibitor (PAI)-1 and reduction of von Willebrand factor (vWF), running wheel activity exerted a different transcriptional response in the vascular tissue of normotensive and hypertensive rats, i.e., lack of reduction of the pro-inflammatory IL-6 in vessels from hypertensive rats. Spironolactone reduced the number of neutrophils; however, in co-presence with high physical activity this effect was blunted. In conclusion, although high physical activity has beneficial effects in normotensive rats, this does not predict similar beneficial effects in the concomitant presence of hypertension and care has to be taken on interactions between pharmacological approaches and high physical activity in hypertensives.

P6372Does modification of activity regimes optimize the effect of high physical activity on hypertensive heart disease?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K.-D Schluter ◽  
R Schreckenberg ◽  
A Wolf ◽  
H Kutsche ◽  
C Troidl ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Life Style ◽  
Work Load ◽  
Running Wheel ◽  
High Physical Activity ◽  
Beneficial Effects ◽  
Active Life ◽  
Free Running ◽  
Wheel Activity

Abstract Aims and background Spontaneously hypertensive rats (SHR) are a suitable model of essential hypertension and allow analyze the progression of hypertension and hypertension-dependent end-organ damage. In this model, acute improvement of physical activity (free running wheel activity) exerts known beneficial effects (such as lowering oxidative stress). However, these initial beneficial effects are lost during the continuation of high physical activity and translate into mal-adaptive processes, suggesting that not any high physical activity exerts beneficial effects. It has been hypothesized that the skeletal muscle release myokines, that contribute to the beneficial effects of exercise. However, myokines, such as IL-6, are induced by an acute increase in work load not by continuous work load. Therefore, we analyzed whether modification of high physical activity, i.e. intermittent free running wheel activity, modify the long-term impact on long lasting hypertension. Methods 38 female SHR aged 6 weeks (pre-hypertensive state) were randomly allocated to one of the following groups: Sedentary (S; standard holding condition) imitating the condition of sedentary life style, high activity (HA; life-long free running wheel) imitating the condition of active life style, temporary activity (TA; 6 months free running wheel and 3 months sedentary) imitating the loss of active life style during ageing, and finally intermittent activity (IA; 10 months repetitive access to running wheels every 4 weeks) imitating altered workloads. All rats were sacrificed at the age of 10 months. Results IA was the only treatment regime that effectively lowered blood pressure (P syst: 186±11 vs. 165±6 mmHg), improved ejection fraction (EF: 56±5 vs. 63±2%), and displayed clear molecular profile of adaptive myocardial hypertrophy rather than mal-adaptive hypertrophy. Moreover, only IA reduced the number of circulating monocytes (377±102 vs. 220±16 /μl), a cell population that immigrated in the left ventricle. The number of monocytes was directly correlated with the expression of MMP12, BNP, ANP, biglycan, collagen-1, actinin, β-MHC, and somatstatin but inversely related to β-adrenoceptor, Glut-4, and UCP3 expression. Finally, IA increased the skeletal expression of IL-6 and decreased the renal expression of AT1 receptors. Conclusion The data confirm the previous findings that not all type of physical activity beneficially affects hypertensive-dependent disease. In contrast, the data support the hypothesis that alterations in work load are required triggering the release of myokines from the skeletal muscle and identify the amount of circulating monocytes as a main trigger of mal-adaptive hypertrophy in these rats. The data are important with respect to optimize life style suggestions for patients with essential hypertension. Acknowledgement/Funding DFG (ERAGON and SFB 1213)

Circadian timekeeping in hyperactive and hypertensive inbred rat strains

1996 ◽  
Vol 271 (3) ◽  
pp. R787-R796 ◽  
Author(s):  
A. M. Rosenwasser ◽  
M. W. Pellowski ◽  
E. D. Hendley
Keyword(s):  
Open Field ◽  
Inbred Strains ◽  
Phase Shifting ◽  
Spontaneously Hypertensive ◽  
Field Activity ◽  
Free Running ◽  
Wistar Kyoto ◽  
Wheel Activity ◽  
Inbred Rat ◽  
Free Running Period

Inbred strains have been used to study genetic and physiological relationships among different aspects of circadian timekeeping, as well as relationships between circadian rhythmicity and other strain-specific traits. The present study characterized several features of circadian timekeeping in genetically hyperactive (WKHA) and genetically hypertensive (WKHT) inbred strains, derived from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. WKHAs and WKHTs differed in free-running period, steady-state entrainment to light-dark cycles, and photic phase shifting, and relationships among these measures were consistent with previous studies of species, strain, and individual differences. Because both WKHTs and SHRs show short circadian periods relative to their respective comparison strains, this trait may cosegregate genetically with hypertension. In contrast, because WKHAs and SHRs show similar photic entrainment and phase shifting, these circadian functions may cosegregate with open-field hyperactivity. Finally, because neither WKHAs nor WKHTs show the SHR's excessive levels of home-cage running wheel activity, this trait is not related to either hypertension or open-field activity. Further work would be required to elucidate specific genetic and/or physiological linkages among these variables.

Influence of genetic background on daily running-wheel activity differs with aging

2005 ◽  
Vol 22 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Michael J. Turner ◽  
Steven R. Kleeberger ◽  
J. Timothy Lightfoot
Keyword(s):  
Physical Activity ◽  
Genetic Background ◽  
Wheel Running ◽  
Inbred Mice ◽  
Inbred Strains ◽  
Broad Sense ◽  
Broad Sense Heritability ◽  
Running Wheel ◽  
Age Related ◽  
Wheel Activity

In humans, physical activity declines with age. We tested the hypothesis that genetic background and age interact to determine daily wheel-running physical activity patterns in mice. Five female mice from ten inbred strains (A/J, AKR/J, Balb/cJ, CBA/J, C3H/HeJ, C3Heb/FeJ, C57Bl/6J, C57L/J, DBA/2J, and SWR/J) were studied for 26 wk starting at 10 wk of age. All mice were housed in separate cages, each with a running wheel and magnetic sensor. Throughout the 26-wk period, age-related change in daily duration ( P < 0.0001), daily distance ( P < 0.0001), and average velocity ( P = 0.0003) differed between the inbred strains. Unlike the other strains, SWR/J mice increased their running-wheel activity throughout the 6-mo time period. Broad-sense heritability estimations for the strains across the 26-wk period ranged between 0.410 and 0.855 for the three physical activity phenotypes. Furthermore, the broad-sense heritability estimates for daily running-wheel distance differed across time and suggested an interaction between genetic background and age on physical activity in these inbred mice.

scholarly journals Low-Intensity physical activity beneficially alters the ultrastructural renal morphology of spontaneously hypertensive rats

Clinics ◽  
2011 ◽  
Vol 66 (5) ◽  
pp. 855-863 ◽  
Author(s):  
Angélica Beatriz Garcia-Pinto ◽  
Verônica Soares de Matos ◽  
Vinicius Rocha ◽  
Jéssica Moraes-Teixeira ◽  
Jorge José Carvalho
Keyword(s):  
Physical Activity ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Low Intensity ◽  
Renal Morphology ◽  
Intensity Physical Activity

Influence of running wheel activity on free-running sleep/wake and drinking circadian rhythms in mice

1991 ◽  
Vol 50 (2) ◽  
pp. 373-378 ◽  
Author(s):  
Dale M. Edgar ◽  
Thomas S. Kilduff ◽  
Connie E. Martin ◽  
William C. Dement
Keyword(s):  
Circadian Rhythms ◽  
Running Wheel ◽  
Free Running ◽  
Wheel Activity

scholarly journals Combination of Hypertension and High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways

2017 ◽  
Author(s):  
Yuan Yuan ◽  
Hisao Naito ◽  
Kazuya Kitamori ◽  
Tamie Nakajima
Keyword(s):  
Transforming Growth Factor ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
High Fat ◽  
Hypertensive Rats ◽  
Nf Kappa B ◽  
Spontaneously Hypertensive ◽  
Hepatic Expression ◽  
Mitogen Activated Protein ◽  
Wistar Kyoto

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-&beta;1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

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